[HTML][HTML] HIF-1α is required for solid tumor formation and embryonic vascularization

HE Ryan, J Lo, RS Johnson - The EMBO journal, 1998 - embopress.org
HE Ryan, J Lo, RS Johnson
The EMBO journal, 1998embopress.org
The transcriptional response to lowered oxygen levels is mediated by the hypoxia-inducible
transcription factor (HIF-1), a heterodimer consisting of the constitutively expressed aryl
hydrocarbon receptor nuclear translocator (ARNT) and the hypoxic response factor HIF-1α.
To study the role of the transcriptional hypoxic response in vivo we have targeted the murine
HIF-1α gene. Loss of HIF-1α in embryonic stem (ES) cells dramatically retards solid tumor
growth; this is correlated with a reduced capacity to release the angiogenic factor vascular …
The transcriptional response to lowered oxygen levels is mediated by the hypoxia-inducible transcription factor (HIF-1), a heterodimer consisting of the constitutively expressed aryl hydrocarbon receptor nuclear translocator (ARNT) and the hypoxic response factor HIF-1α. To study the role of the transcriptional hypoxic response in vivo we have targeted the murine HIF-1α gene. Loss of HIF-1α in embryonic stem (ES) cells dramatically retards solid tumor growth; this is correlated with a reduced capacity to release the angiogenic factor vascular endothelial growth factor (VEGF) during hypoxia. HIF-1α null mutant embryos exhibit clear morphological differences by embryonic day (E) 8.0, and by E8. 5 there is a complete lack of cephalic vascularization, a reduction in the number of somites, abnormal neural fold formation and a greatly increased degree of hypoxia (measured by the nitroimidazole EF5). These data demonstrate the essential role of HIF-1α in controlling both embryonic and tumorigenic responses to variations in microenvironmental oxygenation.
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